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Transplant immunology

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https://www.readbyqxmd.com/read/28088784/a-phase-i-clinical-study-of-autologous-dendritic-cell-therapy-in-patients-with-relapsed-or-refractory-multiple-myeloma
#1
Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Joon Haeng Rhee, Frank Emmrich, Je-Jung Lee
Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088653/immune-stimulation-during-chemotherapy-increases-incidence-of-acute-graft-versus-host-disease-in-acute-myeloid-leukemia-a-study-on-behalf-of-sfgm-tc-and-alfa
#2
Lining Wang, Emmanuel Raffoux, Xavier Thomas, Ibrahim Yakoub-Agha, Jean-Henri Bouhris, Stéphane de Botton, Mauricette Michallet, Stéphanie Nguyen Quoc, Xavier Troussard, Eric Deconinck, Denis Caillot, Pascal Turlure, Stéphane Vigouroux, Arnaud Pigneux, Anne Huynh, Jean-Valère Malfuson, Michael Loschi, Gerard Socie, Hervé Dombret, Régis Peffault de la Tour, Thomas Cluzeau
60-70% of AML patients have an indication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) during their treatment. Graft versus host disease (GvHD), the major cause of mortality and comorbidities post-transplantation, develops by immunological mechanism and decides greatly prognosis and quality of life (QoL) of graft recipient. Current GvHD prophylaxis is not personalized. Infections, toxicities and leukemic infiltration complicate the first chemotherapy phases prior to allo-HSCT. They, to certain extent, induce local immune stimulation...
January 5, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28067566/basic-concepts-in-kidney-transplant-immunology
#3
Roberta Callus, Jesmar Buttigieg, Andrei Agius Anastasi, Ahmed Halawa
Advances in the field of immunohistocompatibility and immunogenetics have been crucial for improvements in kidney transplant outcomes. This review provides a practical outline of these important breakthroughs for the general physician, at a time when demand for kidney transplants is increasing.
January 2, 2017: British Journal of Hospital Medicine
https://www.readbyqxmd.com/read/28060025/antibody-mediated-rejection-what-is-the-clinical-relevance
#4
Rachel Hogen, Joseph DiNorcia, Kiran Dhanireddy
PURPOSE OF REVIEW: The review outlines the diagnosis, clinical implications, and treatment strategies for acute and chronic antibody-mediated rejection (AMR) after orthotopic liver transplantation (OLT). RECENT FINDINGS: A combination of clinical work-up, histopathology, C4d staining, and donor-specific antibody (DSA) should be used to diagnose AMR. The differential diagnosis for idiopathic fibrosis now includes chronic AMR. Characterization of pathogenic DSA continues to progress...
January 3, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28058228/corticosteroid-minimization-in-renal-transplantation-careful-patient-selection-enables-feasibility
#5
Georgios Vlachopanos, Julie M Bridson, Ajay Sharma, Ahmed Halawa
AIM: To explore the benefits and harms of corticosteroid (CS) minimization following renal transplantation. METHODS: CS minimization attempts to improve cardiovascular risk factors (hypertension, diabetes, dyslipidemia), to enhance growth in children, to ameliorate bone disease and to lead to better compliance with immunosuppressive agents. Nevertheless, any benefit must be carefully weighed against the reduction in net immunosuppression and the potential harm to renal allograft function and survival...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28057639/clinical-and-immunologic-impact-of-ccr5-blockade-in-graft-versus-host-disease-prophylaxis
#6
Ryan H Moy, Austin P Huffman, Lee P Richman, Lisa Crisalli, Ximi K Wang, James A Hoxie, Rosemarie Mick, Stephen G Emerson, Yi Zhang, Robert H Vonderheide, David L Porter, Ran Reshef
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Lymphocyte trafficking via chemokine receptors such as CCR5 plays a critical role in alloreactive responses, and previous data suggest that CCR5 blockade with maraviroc results in a low incidence of visceral GVHD. However, the full scope of clinical and immunologic effects of CCR5 blockade in HSCT has not been described. We compared a cohort of patients enrolled on a trial of reduced-intensity allo-HSCT with standard GVHD prophylaxis plus maraviroc to a contemporary control cohort receiving standard GVHD prophylaxis alone...
January 5, 2017: Blood
https://www.readbyqxmd.com/read/28057181/immunoth%C3%A3-rapie-et-greffe-de-cellules-souches-h%C3%A3-matopo%C3%A3-%C3%A3-tiques-allog%C3%A3-niques
#7
Flore Sicre de Fontbrune, Doriane Cavalieri, Mathieu Leclerc, Florence Beckerich, Sébastien Maury, Régis Peffault de Latour, Stéphanie N-Guyen, Jacques-Olivier Bay
Allogeneic stem cell transplantations represent perfect example of immunotherapy. Its positive aspects are due to the graft versus tumor effect. Unfortunately, this therapeutic advantage is usually associated with graft versus host effects. While the mechanism of these two graft reactions remain unclear, this is possible to modulate these immunologic effects. The type of conditioning regimen, the source of donor and the use of donor cells after the transplantation may influence the toxicity and the tumor response, leading to a better optimization of the procedure...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28056461/predicting-post-transplant-recurrence-of-iga-nephropathy-the-importance-of-crescents
#8
Rupali S Avasare, Paul E Rosenstiel, Ziad S Zaky, Demetra S Tsapepas, Gerald B Appel, Glen S Markowitz, Andrew S Bomback, Pietro A Canetta
BACKGROUND: Most studies that have assessed the predictors of recurrent IgA nephropathy (IgAN) in the renal allograft have focused on post-transplant features. Identifying high-risk pre-transplant features of IgAN is useful for counseling patients and may help in tailoring post-transplant immunosuppression. METHODS: We investigated the pre-transplant clinical and biopsy features of 62 patients with IgAN who received transplants at Columbia University Medical Center from 2001 to 2012 and compared the characteristics and outcomes of patients with IgAN recurrence to those without recurrence...
January 6, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28055100/exposure-stress-induces-reversible-corneal-graft-opacity-in-recipients-with-herpes-simplex-virus-1-infections
#9
Alexander M Rowe, Hongmin Yun, Robert L Hendricks
Purpose: Most of the inflammation in murine herpes simplex virus type 1 (HSV-1)-induced stromal keratitis (HSK) is due to exposure stress resulting from loss of corneal nerves and blink reflex. Corneal grafts often fail when placed on corneal beds with a history of HSK. We asked if corneal exposure contributes to the severe pathology of corneal grafts on HSV-1-infected corneal beds. Methods: Herpes simplex virus type 1-infected corneas were tested for blink reflex...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28052693/safety-and-efficacy-of-ex-vivo-donor-lung-adenoviral-il-10-gene-therapy-in-a-large-animal-lung-transplant-survival-model
#10
Tiago Noguchi Machuca, Marcelo Cypel, Riccardo Bonato, Jonathan C Yeung, Yi-Min Chun, Stephen Juvet, Guan Zehong, David M Hwang, Manyin Chen, Tomohito Saito, Constantine Harmantas, Beverly Davidson, Thomas K Waddell, Mingyao Liu, Shaf Keshavjee
OBJECTIVE: Ex vivo normothermic lung perfusion (EVLP) is a novel platform and method developed to facilitate functional assessment and implementation of advanced therapies for donor lungs prior to transplantation. We aimed to determine the safety and immunological and functional benefits of ex vivo adenoviral human IL-10 (AdhIL-10) gene delivery to prevent the development of primary graft dysfunction in a large animal survival model. METHODS: Pig donor lungs were retrieved, preserved for 6 hours at 4oC and then randomly assigned to 4 groups: 1) AdhIL-10 Gene Therapy: 12 hours EVLP + AdhIL-10 intra-bronchial delivery; 2) EVLP-control: 12 hours EVLP; 3) Vector-control: 12 hours EVLP + adenoviral vector intra-bronchial delivery; and 4) Prolonged hypothermic preservation: Additional 12 hours of cold ischemia...
January 4, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28044415/modulation-of-alloimmune-response-by-commensal-gut-microbiota-and-potential-new-avenues-to-influence-the-outcome-of-allogeneic-transplantation-by-modification-of-the-gut-culture
#11
REVIEW
S Kanangat
Host defence response against microbial infections was the foundation for the Science of Immunology. Now, we know the mechanisms of such host defence which include innate immune responses that is generally nonspecific but effective in many cases and lead to more specific responses called adaptive immune response. The gene loci of class I, II and III of the major histocompatibility complex (MHC) play a major role in directing the adaptive immune responses by presenting processed antigens to T and B cells to induce appropriate antigen-specific cellular and or humoral immune responses...
January 3, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28042143/mesenchymal-stem-cells-ameliorate-b-cell-mediated-immune-responses-and-increase-il-10-expressing-regulatory-b-cells-in-an-ebi3-dependent-manner
#12
Kyung-Ah Cho, Jun-Kyu Lee, Yu-Hee Kim, Minhwa Park, So-Youn Woo, Kyung-Ha Ryu
Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells, producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue. Conversely, IL-10-producing regulatory B (Breg) cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease. Thus, regulating the equilibrium between antibody-producing effector B cells and Breg cells is critical for the treatment of autoimmune disease...
January 2, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28028357/can-probiotics-benefit-children-with-autism-spectrum-disorders
#13
REVIEW
Fernando Navarro, Yuying Liu, Jon Marc Rhoads
Children with autism are commonly affected by gastrointestinal problems such as abdominal pain, constipation and diarrhea. In recent years, there has been a growing interest in the use of probiotics in this population, as it hypothetically may help to improve bowel habits and the behavioral and social functioning of these individuals. The gut microbiome plays an important role in the pathophysiology of organic as well as functional gastrointestinal disorders. Microbial modification with the use of antibiotics, probiotics, and fecal transplantation have been effective in the treatment of conditions such as recurrent Clostridium difficile infection, pouchitis, and irritable bowel syndrome...
December 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28011186/nk-cells-are-biologic-and-biochemical-targets-of-6-mercaptopurine-in-crohn-s-disease-patients
#14
Susy Yusung, Dermot McGovern, Lin Lin, Daniel Hommes, Venu Lagishetty, Jonathan Braun
NK cells, which contribute to immune defense against certain viral infections and neoplasia, are emerging as modifiers of chronic immunologic diseases including transplant rejection and autoimmune diseases. Immunobiology and genetic studies have implicated NK cells as a modifier of Crohn's disease, a condition often treated with thiopurine agents such as 6-mercaptopurine (6-MP). Here, we demonstrate that thiopurines mediate NK cell apoptosis via a caspase 3 and 9 inclusive pathway, and that this process is triggered by thiopurine-mediated inhibition of Rac1...
December 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28008595/defective-expression-of-apoptosis-related-molecules-in-multiple-sclerosis-patients-is-normalized-early-after-autologous-haematopoietic-stem-cell-transplantation
#15
G L V de Oliveira, A F Ferreira, E P L Gasparotto, S Kashima, D T Covas, C T Guerreiro, D G Brum, A A Barreira, J C Voltarelli, B P Simões, M C Oliveira, F A de Castro, K C R Malmegrim
Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts...
November 7, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28008169/advances-in-islet-encapsulation-technologies
#16
Tejal Desai, Lonnie D Shea
Type 1 diabetes is an autoimmune disorder in which the immune system attacks and destroys insulin-producing islet cells of the pancreas. Although islet transplantation has proved to be successful for some patients with type 1 diabetes, its widespread use is limited by islet donor shortage and the requirement for lifelong immunosuppression. An encapsulation strategy that can prevent the rejection of xenogeneic islets or of stem cell-derived allogeneic islets can potentially eliminate both of these barriers. Although encapsulation technology has met several challenges, the convergence of expertise in materials, nanotechnology, stem cell biology and immunology is allowing us to get closer to the goal of encapsulated islet cell therapy for humans...
December 23, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28007665/cd25-blockade-delays-regulatory-t-cell-reconstitution-and-does-not-prevent-graft-versus-host-disease-after-allogeneic-hematopoietic-cell-transplantation
#17
Frederick L Locke, Joseph Pidala, Barry Storer, Paul J Martin, Michael A Pulsipher, Thomas R Chauncey, Niels Jacobsen, Nicolaus Kröger, Irwin Walker, Susan Light, Bronwen E Shaw, Francisca Beato, Ginna G Laport, Auayporn Nademanee, Armand Keating, Gerard Socie, Claudio Anasetti
Daclizumab, a humanized monoclonal antibody, binds CD25 and blocks formation of the IL-2 receptor on T cells. A study of daclizumab as acute graft-versus-host disease (GVHD) prophylaxis after unrelated bone marrow transplantation was conducted before the importance of CD25(+)FOXP3(+) regulatory T cells (Tregs) was recognized. Tregs can abrogate the onset of GVHD. The relation between Tregs and a graft-versus-malignancy effect is not fully understood. An international, multicenter, double-blind clinical trial randomized 210 adult or pediatric patients to receive 5 weekly doses of daclizumab at 0...
December 19, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28006867/differential-profile-of-activated-regulatory-t-cell-subsets-and-micrornas-in-tolerant-liver-transplant-recipients
#18
B Revilla-Nuin, A de Bejar, L Martínez-Alarcón, J I Herrero, C M Martínez-Cáceres, P Ramírez, A Baroja-Mazo, J A Pons
: Regulatory T cells (Tregs) play a potential role in operational tolerance in liver transplant patients, and microRNAs (miRNAs) are known to be involved in immunological responses and tolerance. Thus, we analyzed the implication of different peripheral blood Treg subsets and miRNAs on liver transplantation tolerance in 24 tolerant (Tol) and 23 non-tolerant (non-Tol) liver transplant recipients by cellular, genetic and epigenetic approximation. Non-Tol patients had a lower demethylation rate of the FOXP3 Treg-specific demethylated region (TSDR) than Tol patients that correlated with the frequency of circulating Tregs...
December 22, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/28003816/hla-mismatching-strategies-for-solid-organ-transplantation-a-balancing-act
#19
REVIEW
Andrea A Zachary, Mary S Leffell
HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27998825/hematopoietic-arginase-1-deficiency-results-in-decreased-leukocytosis-and-increased-foam-cell-formation-but-does-not-affect-atherosclerosis
#20
Baoyan Ren, Erik Van Kampen, Theo J C Van Berkel, Sheena M Cruickshank, Miranda Van Eck
BACKGROUND AND AIMS: Arginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages...
November 16, 2016: Atherosclerosis
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